Raffaella Rosy Vescio

Osteoarthritis (OA) is a leading cause of disability worldwide, characterized by progressive joint degeneration driven by extracellular matrix (ECM) breakdown, chondrocyte apoptosis, and chronic low-grade inflammation. Despite the availability of several pharmacological and non-pharmacological interventions, no current therapy effectively halts or reverses disease progression. Physical activity is traditionally recognized as a cornerstone in OA management, improving pain and functional outcomes; however, the molecular mechanisms underlying its beneficial effects remain partially understood. Irisin, a myokine generated by proteolytic cleavage of fibronectin type III domain-containing protein 5 in response to muscle contraction, has recently emerged as a potential regulator of cartilage homeostasis. Experimental evidence indicates that irisin exerts pleiotropic effects by modulating inflammatory and catabolic signaling pathways, promoting anabolic and reparative processes, restoring autophagic and mitophagic flux, and preserving mitochondrial function. These actions collectively contribute to the maintenance of ECM integrity and chondrocyte viability. In vitro and in vivo studies consistently support the protective role of irisin in cartilage biology, highlighting its involvement in the muscle–cartilage axis and its potential as both a biomarker and therapeutic target for OA. This narrative review critically evaluates the chondrocyte-specific mechanisms, receptor uncertainties, experimental-model limitations, analytical challenges, and delivery strategies that currently define the biological and translational relevance of irisin in OA. Particular attention is given to the identification of irisin-mediated signaling pathways in chondrocytes, optimization of delivery strategies, and the definition of exercise regimens capable of maximizing its chondroprotective effects.

Bloodstream infections (BSIs) represent a major clinical challenge, particularly in patients with suspected sepsis, where rapid pathogen identification is critical for timely and appropriate antimicrobial therapy. Blood culture (BC) remains the reference diagnostic method but is limited by a long turnaround time and reduced sensitivity, especially in patients receiving prior antibiotics. This pilot study aimed to evaluate the diagnostic performance and clinical added value of culture-independent digital PCR (dPCR) performed directly on whole blood compared with paired BC. A total of 37 samples from 27 patients with suspected BSI admitted to a tertiary-care hospital were analyzed. dPCR demonstrated the ability to detect a broader spectrum of pathogens compared with BC (34 vs. 28 species), with improved identification of fastidious organisms and fungi, particularly Candida spp. Diagnostic performance analysis showed a sensitivity of 75.0% and a specificity of 53.8%, with a positive predictive value of 75.0% and a negative predictive value of 53.8%. Likelihood ratios indicated moderate rule-in capability (Likelihood ration positive 1.62) but limited rule-out performance (Likelihood ratio negative 0.46). Importantly, concordance analysis integrating microbiological and clinical data revealed that a substantial proportion of discordant dPCR-positive results were clinically plausible, suggesting detection of infections not captured by BC, particularly in polymicrobial settings, under antibiotic pressure, or in fungal infections. Longitudinal observations further highlighted the potential of dPCR for monitoring pathogen dynamics and treatment response. Overall, dPCR provides rapid and complementary diagnostic information, enabling earlier pathogen detection, identification of antimicrobial resistance markers, and improved characterization of complex infections. While not suitable as a standalone test due to limited negative predictive value, its integration with conventional microbiology may enhance diagnostic accuracy and support antimicrobial stewardship in the management of BSIs.